Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzal... | NCT04934722

ID	Type	Description
MK-3475-991 China Extension	Other Identifier	MSD
KEYNOTE-991	Other Identifier	MSD
jRCT2080225171	Registry Identifier	jRCT

Description Module

Brief Summary

This study will assess the efficacy and safety of pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT in Chinese participants with mHSPC. The primary hypothesis is that in participants with mHSPC, the combination of pembrolizumab plus enzalutamide plus ADT is superior to placebo plus enzalutamide plus ADT with respect to 1) radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR) and 2) overall survival (OS). As of Amendment 4, the study is being stopped for futility. All the prespecified interim analysis after interim analysis (IA1) and final analysis of the study described the statistical analysis plan (SAP) will not be performed. Safety analysis will be performed at the end of the study; there will be no further analyses for efficacy and electronic patient-reported outcome (ePRO) endpoints collected from participants beyond the IA1 cutoff date. All study participants will stop ongoing treatment with pembrolizumab/placebo. Exceptions may be requested for study participants who, in the assessment of their study physician, are benefitting from the combination of enzalutamide and pembrolizumab, after consulting with the Sponsor. All other study participants should be discontinued from study and be offered standard of care (SOC) treatment as deemed necessary by the Investigator. If enzalutamide as SOC is not accessible off study to the participant, central sourcing may continue. As of Amendment 04, disease progression will no longer be centrally verified, participants will only be assessed locally. As of Amendment 4, Second Course treatment is not an option for participants. There are currently no participants in the Second Course Phase.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pembrolizumab + Enzalutamide + ADT	Experimental	Starting on Day 1 of each 21-day cycle, participants receive 200 mg pembrolizumab intravenously (IV) every 3 weeks (Q3W) for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.	Biological: Pembrolizumab Drug: Enzalutamide Drug: Androgen Deprivation Therapy (ADT)
Placebo + Enzalutamide + ADT	Placebo Comparator	Starting on Day 1 of each 21-day cycle, participants receive placebo IV Q3W for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.	Drug: Enzalutamide Drug: Androgen Deprivation Therapy (ADT) Other: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Biological	Pembrolizumab is administered as an IV infusion at 200 mg on Day 1 of each 21-day cycle for up to 35 cycles.	Pembrolizumab + Enzalutamide + ADT

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment.	Up to approximately 17 months
Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.	Up to approximately 17 months

Secondary Outcomes

Measure	Description	Time Frame
Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)	TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product limit (Kaplan-Meier) method for censored data. Participants without documented event at time of analysis will be censored at the date of last known time to have not received subsequent new anti-cancer therapy.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male participants with histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
Has metastatic disease assessed by investigator and verified by BICR by either ≥2 bone lesions on bone scan and/or visceral disease by computed tomography/magnetic resonance imaging (CT/MRI)
Willing to maintain continuous Androgen Deprivation Therapy (ADT) with a luteinizing-hormone releasing hormone (LHRH) agonists or antagonists during study treatment or have a history of bilateral orchiectomy
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 10 days of randomization
Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
Has adequate organ function
Has provided newly obtained core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed). Participants with bone only or bone predominant disease may provide a bone biopsy sample
Male participants must agree to the following during the intervention period and for at least 120 days after the last dose of study intervention: Refrain from donating sperm PLUS either be abstinent from heterosexual intercourse and agree to remain abstinent OR agree to use contraception, unless confirmed to be azoospermic
Male participants must agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex

Exclusion Criteria:

Has a known additional malignancy that is progressing or has required active treatment in the last 3 years
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and not recovered adequately from the toxicities and/or complications
Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules
Has an active infection (including tuberculosis) requiring systemic therapy
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
Has known or suspected central nervous system (CNS) metastases and/or carcinomatous meningitis
Has a history of seizure or any condition that may predispose to seizure
Has a history of loss of consciousness within 12 months of screening
Has had myocardial infarction or uncontrolled angina within 6 months prior to randomization, or has New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure
Has hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or uncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg) at the screening visit
Has a history of clinically significant ventricular arrhythmias
Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostate cancer for >39 months in duration or within 9 months prior to randomization or with evidence of disease progression while receiving ADT
Has had prior treatment with a next generation hormonal agent (eg, abiraterone, enzalutamide, apalutamide, darolutamide)
Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
Has received a live vaccine within 30 days prior to randomization
Has a "superscan" bone scan
Has had an allogenic tissue/solid organ transplant
Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
Has received any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer with the following exceptions:
1. Up to 3 months of ADT or orchiectomy with or without concurrent first-generation antiandrogens, if patient was not treated with docetaxel
2. May have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to randomization
3. For participants with low volume metastatic disease, may have 1 course of definitive radiotherapy if it was administered at least 4 weeks prior to randomization
4. Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of randomization and no evidence of disease progression. In these participants up to 6 months of ADT permitted

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Peking University First Hospital ( Site 0800)		Beijing	Beijing Municipality	100034	China
Beijing Cancer Hospital ( Site 0802)

Label	URL
Merck Clinical Trials Information	View source

ID	Title	Description
FG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	May 15, 2023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment.

All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response

Posted

Median

95% Confidence Interval

Months

Up to approximately 17 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met

Units	Counts
Participants	OG00092 OG00194

Title

Denominators

Categories

Title	Measurements
	OG00014.4(NA to NA)NA = lower limit and upper limit of 95% CI for rPFS cannot be calculated at the time of last disease assessment due to insufficient number of participants with events. OG001NA(NA to NA)NA = Median, lower limit and upper limit of 95% CI for rPFS cannot be calculated at the time of last disease assessment due to insufficient number of participants with events.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Hazard Ratio (HR)	0.74			2-Sided	95	0.24	2.34			HR and associated 95% Confidence Interval (CI) were calculated using Cox regression model with Efron's method of tie handling with treatment as a covariate.		Other

Primary

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.

All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response

Posted

Median

95% Confidence Interval

Months

Up to approximately 17 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met

Secondary

Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)

TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product limit (Kaplan-Meier) method for censored data. Participants without documented event at time of analysis will be censored at the date of last known time to have not received subsequent new anti-cancer therapy.

All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response.

Posted

Median

95% Confidence Interval

Months

Up to Approximately 17 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met

Secondary

Time to First Symptomatic Skeletal-related Event (TTSSRE)

TTSSRE was the time from randomization to the first symptomatic skeletal-related event defined as: use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathologic bone fracture (vertebral or nonvertebral), occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention, whichever occurs first. The TTSSRE was calculated using the Kaplan-Meier method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment.

All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response.

Posted

Median

95% Confidence Interval

Months

Up to Approximately 17 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met

Secondary

Time to Prostate-specific Antigen (PSA) Progression

Time to PSA progression was the time from randomization to PSA progression. The PSA progression date was defined as the date of 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, or 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline. Time to PSA was calculated using Kaplan-Meier method for censored data. Participants without PSA progression were censored at the last PSA date.

All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response

Posted

Median

95% Confidence Interval

Months

Up to Approximately 17 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met

Secondary

Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR

The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered progression. Time to radiographic soft tissue progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment.

All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response

Posted

Median

95% Confidence Interval

Months

Up to Approximately 17 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT

Secondary

Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item #3 ("Worst Pain in 24 Hours") and Opiate Use

TTPP was defined as the time from randomization to pain progression as determined by Item 3 of the BPI-SF. Pain progression was defined as: 1) For participants asymptomatic at baseline: a >2-point change from baseline in the average BPI-SF item 3 score at 2 consecutive visits or initiation of opioid use for pain 2) For participants symptomatic at baseline (average BPI-SF Item 3 score >0 and/or currently taking opioids; a >2-point change from baseline in the average BPI-SF Item 3 score and the average worst pain score >4 and no decrease in average opioid use. TTPP was calculated using the Kaplan-Meier method for censored data. Participants who had > 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment.

All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion who received at least one dose of study treatment, and who had at least 1 BPI-SF assessment

Posted

Median

95% Confidence Interval

Months

Up to Approximately 17 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.

Secondary

Time From Randomization to Disease Progression as Determined by Investigator Assessment After Next-line of Therapy or Death From Any Cause, Whichever Occurs First (PFS2)

PFS2 was defined as the time from randomization to disease progression as determined by investigator assessment of radiological or clinical progression after next-line of therapy or death from any cause, whichever occurs first.

All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion that were evaluable for response

Posted

Median

95% Confidence Interval

Months

Up to Approximately 17 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met

Secondary

Prostate-specific Antigen (PSA) Response Rate

PSA response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by >50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed >3 weeks from the original response.

All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion who had a baseline PSA measurement and had data available for analysis

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to Approximately 17 Months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met

Secondary

Prostate-specific Antigen (PSA) Undetectable

PSA undetectable rate was defined as the percentage of participants with detectable PSA (> 0.2 ng/mL) at baseline, which becomes undetectable (< 0.2 ng/mL) during study treatment.

All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion with detectable PSA at baseline and had data available for analysis

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to Approximately 17 Months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met

Secondary

Objective Response Rate (ORR) Per PCWG-Modified RECIST 1.1 as Assessed by BICR

ORR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on base scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG).

All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion with measurable disease at baseline and had data available for analysis

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to Approximately 17 Months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met

Secondary

Duration of Response (DOR) Per PCWG- Modified RECIST 1.1 as Assessed by BICR

DOR was defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of a least 5 mm. PD per PCWG was the appearance of >2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and were persistent for >6 weeks. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data.

All Chinese participants who were randomized to the global study (NCT04191096) or to the extension portion who demonstrated a CR or PR, and had data available for analysis

Posted

Median

95% Confidence Interval

Months

Up to Approximately 17 Months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT

Secondary

Number of Participants Who Experience an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Participants who experienced an AE will be reported for each arm.

Not Posted

Jun 2027

Up to Approximately 17 Months

Participants

Secondary

Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported for each arm.

Not Posted

Jun 2027

Up to Approximately 17 Months

Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected94 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Autoimmune myocarditis	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Myocardial infarction	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Hypophysitis	Endocrine disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Immune-mediated thyroiditis	Endocrine disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Anal incontinence	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected94 at risk
Gastrointestinal ulcer perforation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Upper gastrointestinal perforation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected94 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected94 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected92 at risk EG0010 events0 affected94 at risk
Septic shock	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected94 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected94 at risk
Brain contusion	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected94 at risk
Neutrophil count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Platelet count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected92 at risk EG0010 events0 affected94 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected94 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected94 at risk
Oesophageal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected94 at risk
Cerebral infarction	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Dizziness	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Insomnia	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Immune-mediated nephritis	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected94 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected94 at risk
Immune-mediated lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Immune-mediated dermatitis	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk
Aortic dissection	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected94 at risk
Thrombosis	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected94 at risk
Venous thrombosis limb	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected94 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG00034 events25 affected92 at risk EG00119 events14 affected94 at risk
Hypothyroidism	Endocrine disorders	MedDRA 26.0	Systematic Assessment	EG0009 events9 affected92 at risk EG0016 events4 affected94 at risk
Constipation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0007 events7 affected92 at risk EG0016 events6 affected94 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00010 events8 affected92 at risk EG0018 events7 affected94 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0004 events4 affected92 at risk EG0017 events7 affected94 at risk
Toothache	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0004 events3 affected92 at risk EG0016 events6 affected94 at risk
Fatigue	General disorders	MedDRA 26.0	Systematic Assessment	EG0009 events9 affected92 at risk EG0018 events7 affected94 at risk
Malaise	General disorders	MedDRA 26.0	Systematic Assessment	EG00010 events10 affected92 at risk EG0015 events4 affected94 at risk
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment	EG0008 events8 affected92 at risk EG0012 events2 affected94 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected92 at risk EG0015 events5 affected94 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0005 events5 affected92 at risk EG0018 events8 affected94 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG00020 events18 affected92 at risk EG00122 events21 affected94 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG00016 events14 affected92 at risk EG00117 events17 affected94 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0005 events5 affected92 at risk EG0016 events5 affected94 at risk
Blood bilirubin increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0005 events4 affected92 at risk EG0019 events5 affected94 at risk
Blood cholesterol increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0007 events6 affected92 at risk EG0012 events2 affected94 at risk
Blood thyroid stimulating hormone increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0006 events5 affected92 at risk EG00110 events8 affected94 at risk
Lymphocyte count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected92 at risk EG0016 events5 affected94 at risk
Neutrophil count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0009 events5 affected92 at risk EG0018 events1 affected94 at risk
Platelet count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG00019 events10 affected92 at risk EG00117 events10 affected94 at risk
Weight decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0004 events4 affected92 at risk EG0015 events5 affected94 at risk
Weight increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0008 events8 affected92 at risk EG00115 events12 affected94 at risk
White blood cell count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG00012 events7 affected92 at risk EG00110 events5 affected94 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG00011 events11 affected92 at risk EG0015 events5 affected94 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0007 events5 affected92 at risk EG0015 events4 affected94 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG00026 events16 affected92 at risk EG00133 events20 affected94 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0005 events4 affected92 at risk EG0018 events6 affected94 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG00013 events8 affected92 at risk EG0019 events7 affected94 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0008 events6 affected92 at risk EG0015 events4 affected94 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0008 events5 affected92 at risk EG0017 events6 affected94 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0008 events7 affected92 at risk EG0019 events6 affected94 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG00010 events4 affected92 at risk EG0017 events6 affected94 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0009 events7 affected92 at risk EG0013 events3 affected94 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG00010 events8 affected92 at risk EG00115 events11 affected94 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected92 at risk EG00110 events9 affected94 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0009 events8 affected92 at risk EG0019 events8 affected94 at risk
Dizziness	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00011 events9 affected92 at risk EG0017 events7 affected94 at risk
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0007 events5 affected92 at risk EG0011 events1 affected94 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0007 events5 affected92 at risk EG0015 events5 affected94 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0006 events5 affected92 at risk EG0013 events3 affected94 at risk
Immune-mediated dermatitis	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0008 events7 affected92 at risk EG0010 events0 affected94 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0006 events6 affected92 at risk EG0014 events4 affected94 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG00029 events23 affected92 at risk EG00110 events9 affected94 at risk
Hot flush	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0008 events8 affected92 at risk EG0019 events9 affected94 at risk
Hypertension	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG00016 events14 affected92 at risk EG00115 events11 affected94 at risk

ID	Term
D006727	Hormone Antagonists
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D045505	Physiological Effects of Drugs
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses

ID	Title	Description
BG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
BG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	4	92	24	92	79	92
EG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met	3	94	10	94	79	94

ID	Term
C582435	pembrolizumab
C540278	enzalutamide
D000726	Androgen Antagonists